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Platelet activity and cardiovascular risk in apparently healthy individuals: a review of the data

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Abstract

Cardiovascular disease is a major cause of morbidity and mortality. Numerous risk scores exist to identify healthy individuals at increased risk of developing cardiovascular disease. Although platelets are a key mediator in the pathogenesis of cardiovascular disease, the role of platelet activity measurements and the incidence of cardiovascular disease are uncertain. Platelet aggregometry—the most well studied method of platelet function testing—is associated with risk factors for cardiovascular disease. However, data supporting platelet aggregation and incident cardiovascular disease is conflicting. Plasma markers of platelet activation are promising candidates. Soluble CD40L and P-selectin are easily measured with a standardized ELISA, and there is some data to suggest an association with cardiovascular disease, but further studies are required. While mean platelet volume is a promising candidate, platelet count and bleeding time are not specific for platelet activity nor are they associated with cardiovascular disease in a healthy population. For this field to progress, we recommend large-scale, prospective studies that measure a battery of these platelet function tests in individuals without cardiovascular disease to better understand the associations, if any, between platelet activity and cardiovascular disease.

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References

  1. 1.

    Berger JS, Jordan CO, Lloyd-Jones D, Blumenthal RS (2010) Screening for cardiovascular risk in asymptomatic patients. J Am Coll Cardiol 55:1169–1177

  2. 2.

    Davi G, Patrono C (2007) Platelet activation and atherothrombosis. N Engl J Med 357:2482–2494

  3. 3.

    Vorchheimer DA, Becker R (2006) Platelets in atherothrombosis. Mayo Clin Proc 81:59–68

  4. 4.

    Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler ER, Reilly MP, Berger JS (2010) Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis. J Thromb Haemost 8:148–156

  5. 5.

    Gurbel PA, Becker RC, Mann KG, Steinhubl SR, Michelson AD (2007) Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 50:1822–1834

  6. 6.

    Heeschen C, Dimmeler S, Hamm CW, van den Brand MJ, Boersma E, Zeiher AM, Simoons ML (2003) Soluble CD40 ligand in acute coronary syndromes. N Engl J Med 348:1104–1111

  7. 7.

    Trip MD, Cats VM, van Capelle FJ, Vreeken J (1990) Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 322:1549–1554

  8. 8.

    Elwood PC, Beswick A, Pickering J, McCarron P, O’Brien JR, Renaud SR, Flower RJ (2001) Platelet tests in the prediction of myocardial infarction and ischaemic stroke: evidence from the caerphilly prospective study. Br J Haematol 113:514–520

  9. 9.

    Sharp DS, Bath PMW, Martin JF, Beswick AD, Sweetnam PM (1994) Platelet and erythrocyte volume and count: epidemiological predictors of impedance measured adp-induced platelet aggregation in whole blood. Platelets 5:6

  10. 10.

    Breddin HK (2005) Can platelet aggregometry be standardized? Platelets 16:151–158

  11. 11.

    Sharp DS, Beswick AD, O’Brien JR, Renaud S, Yarnell JW, Elwood PC (1990) The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the caerphilly collaborative heart disease study. Thromb Haemost 64:211–215

  12. 12.

    Yee DL, Sun CW, Bergeron AL, Dong JF, Bray PF (2005) Aggregometry detects platelet hyperreactivity in healthy individuals. Blood 106:2723–2729

  13. 13.

    Yee DL, Bergeron AL, Sun CW, Dong JF, Bray PF (2006) Platelet hyperreactivity generalizes to multiple forms of stimulation. J Thromb Haemost 4:2043–2050

  14. 14.

    Breddin HK, Lippold R, Bittner M, Kirchmaier CM, Krzywanek HJ, Michaelis J (1999) Spontaneous platelet aggregation as a predictive risk factor for vascular occlusions in healthy volunteers? Results of the HAPARG Study. Haemostatic parameters as risk factors in healthy volunteers. Atherosclerosis 144:211–219

  15. 15.

    Thaulow E, Erikssen J, Sandvik L, Stormorken H, Cohn PF (1991) Blood platelet count and function are related to total and cardiovascular death in apparently healthy men. Circulation 84:613–617

  16. 16.

    Meade TW, Cooper JA, Miller GJ (1997) Platelet counts and aggregation measures in the incidence of ischaemic heart disease (IHD). Thromb Haemost 78:926–929

  17. 17.

    Elwood PC, Renaud S, Beswick AD, O’Brien JR, Sweetnam PM (1998) Platelet aggregation and incident ischaemic heart disease in the Caerphilly cohort. Heart 80:578–582

  18. 18.

    Sharp DS, Ben-Shlomo Y, Beswick AD, Andrew ME, Elwood PC (2005) Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited. Platelets 16:320–328

  19. 19.

    van der Loo B, Martin JF (1999) A role for changes in platelet production in the cause of acute coronary syndromes. Arterioscler Thromb Vasc Biol 19:672–679

  20. 20.

    Bath PM, Butterworth RJ (1996) Platelet size: measurement, physiology and vascular disease. Blood Coagul Fibrinolysis 7:157–161

  21. 21.

    Endler G, Klimesch A, Sunder-Plassmann H, Schillinger M, Exner M, Mannhalter C, Jordanova N, Christ G, Thalhammer R, Huber K, Sunder-Plassmann R (2002) Mean platelet volume is an independent risk factor for myocardial infarction but not for coronary artery disease. Br J Haematol 117:399–404

  22. 22.

    Senaran H, Ileri M, Altinbas A, Kosar A, Yetkin E, Ozturk M, Karaaslan Y, Kirazli S (2001) Thrombopoietin and mean platelet volume in coronary artery disease. Clin Cardiol 24:405–408

  23. 23.

    Braekkan SK, Mathiesen EB, Njolstad I, Wilsgaard T, Stormer J, Hansen JB (2010) Mean platelet volume is a risk factor for venous thromboembolism: the Tromso Study, Tromso, Norway. J Thromb Haemost 8:157–162

  24. 24.

    Klovaite J, Benn M, Yazdanyar S, Nordestgaard BG (2010). High platelet volume and increased risk of myocardial infarction: 39,531 participants from the general population. J Thromb Haemost

  25. 25.

    Buckley MF, James JW, Brown DE, Whyte GS, Dean MG, Chesterman CN, Donald JA (2000) A novel approach to the assessment of variations in the human platelet count. Thromb Haemost 83:480–484

  26. 26.

    Pizzi C, De Stavola BL, Meade TW (2010) Long-term association of routine blood count (Coulter) variables on fatal coronary heart disease: 30 year results from the first prospective Northwick Park Heart Study (NPHS-I). Int J Epidemiol 39:256–265

  27. 27.

    Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE (1997) Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 96:1102–1108

  28. 28.

    Folsom AR, Rosamond WD, Shahar E, Cooper LS, Aleksic N, Nieto FJ, Rasmussen ML, Wu KK (1999) Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 100:736–742

  29. 29.

    van der Bom JG, Heckbert SR, Lumley T, Holmes CE, Cushman M, Folsom AR, Rosendaal FR, Psaty BM (2009) Platelet count and the risk for thrombosis and death in the elderly. J Thromb Haemost 7:399–405

  30. 30.

    Michelson AD, Frelinger AL 3rd, Furman MI (2006) Current options in platelet function testing. Am J Cardiol 98:4N–10N

  31. 31.

    Rodgers RP, Levin J (1990) A critical reappraisal of the bleeding time. Semin Thromb Hemost 16:1–20

  32. 32.

    Milner PC, Martin JF (1985) Shortened bleeding time in acute myocardial infarction and its relation to platelet mass. Br Med J (Clin Res Ed) 290:1767–1770

  33. 33.

    O’Brien JR, Jamieson S, Etherington M, Klaber MR, Ainsworth JF (1973) Stressed template bleeding-time and other platelet-function tests in myocardial infarction. Lancet 1:694–696

  34. 34.

    Elwood PC, Pickering J, Yarnell J, O’Brien JR, Ben Shlomo Y, Bath P (2003) Bleeding time, stroke and myocardial infarction: the Caerphilly prospective study. Platelets 14:139–141

  35. 35.

    Johnson-Tidey RR, McGregor JL, Taylor PR, Poston RN (1994) Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1. Am J Pathol 144:952–961

  36. 36.

    Ridker PM, Buring JE, Rifai N (2001) Soluble P-selectin and the risk of future cardiovascular events. Circulation 103:491–495

  37. 37.

    Cleanthis M, Smout J, Bhattacharya V, Ashour H, Dyker A, Ford GA, Mikhailidis DP, Stansby GP (2008) Soluble but not platelet P-selectin correlates with spontaneous platelet aggregation: a pilot study. Clin Appl Thromb Hemost 14:227–233

  38. 38.

    Ikeda H, Takajo Y, Ichiki K, Ueno T, Maki S, Noda T, Sugi K, Imaizumi T (1995) Increased soluble form of P-selectin in patients with unstable angina. Circulation 92:1693–1696

  39. 39.

    Sakurai S, Inoue A, Koh CS, Owa M, Yanagisawa N (1997) Soluble form of selectins in blood of patients with acute myocardial infarction and coronary intervention. Vasc Med 2:163–168

  40. 40.

    Blann AD, Nadar SK, Lip GY (2003) The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J 24:2166–2179

  41. 41.

    Reiner AP, Carlson CS, Thyagarajan B, Rieder MJ, Polak JF, Siscovick DS, Nickerson DA, Jacobs DR Jr, Gross MD (2008) Soluble P-selectin, SELP polymorphisms, and atherosclerotic risk in European-American and African-African young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Arterioscler Thromb Vasc Biol 28:1549–1555

  42. 42.

    Malik I, Danesh J, Whincup P, Bhatia V, Papacosta O, Walker M, Lennon L, Thomson A, Haskard D (2001) Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet 358:971–976

  43. 43.

    Schonbeck U, Varo N, Libby P, Buring J, Ridker PM (2001) Soluble CD40L and cardiovascular risk in women. Circulation 104:2266–2268

  44. 44.

    Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G, Kroczek RA (1998) CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 391:591–594

  45. 45.

    Andre P, Prasad KS, Denis CV, He M, Papalia JM, Hynes RO, Phillips DR, Wagner DD (2002) CD40L stabilizes arterial thrombi by a β3 integrin–dependent mechanism. Nat Med 8:247–252

  46. 46.

    Prasad KS, Andre P, He M, Bao M, Manganello J, Phillips DR (2003) Soluble CD40 ligand induces β3 integrin tyrosine phosphorylation and triggers platelet activation by outside-in signaling. Proc Natl Acad Sci USA 100:12367–12371

  47. 47.

    Riondino S, Martini F, La Farina F, Spila A, Guadagni F, Ferroni P (2010) Increased plasma levels of soluble CD40 ligand correlate with platelet activation markers and underline the need for standardized pre-analytical conditions. Clin Biochem 43:666–670

  48. 48.

    Vishnevetsky D, Kiyanista VA, Gandhi PJ (2004) CD40 ligand: a novel target in the fight against cardiovascular disease. Ann Pharmacother 38:1500–1508

  49. 49.

    Ferro D, Loffredo L, Polimeni L, Fimognari F, Villari P, Pignatelli P, Fuster V, Violi F (2007) Soluble CD40 ligand predicts ischemic stroke and myocardial infarction in patients with nonvalvular atrial fibrillation. Arterioscler Thromb Vasc Biol 27:2763–2768

  50. 50.

    Novo S, Basili S, Tantillo R, Falco A, Davi V, Novo G, Corrado E, Davi G (2005) Soluble CD40L and cardiovascular risk in asymptomatic low-grade carotid stenosis. Stroke 36:673–675

  51. 51.

    Smyth EM (2010) Thromboxane and the thromboxane receptor in cardiovascular disease. Clin Lipidol 5:209–219

  52. 52.

    Vejar M, Fragasso G, Hackett D, Lipkin DP, Maseri A, Born GV, Ciabattoni G, Patrono C (1990) Dissociation of platelet activation and spontaneous myocardial ischemia in unstable angina. Thromb Haemost 63:163–168

  53. 53.

    Fitzgerald DJ, Roy L, Catella F, FitzGerald GA (1986) Platelet activation in unstable coronary disease. N Engl J Med 315:983–989

  54. 54.

    Thachil J (2010) The prothrombotic potential of platelet factor 4. Eur J Intern Med 21:79–83

  55. 55.

    Nassar T, Sachais BS, Akkawi S, Kowalska MA, Bdeir K, Leitersdorf E, Hiss E, Ziporen L, Aviram M, Cines D, Poncz M, Higazi AA (2003) Platelet factor 4 enhances the binding of oxidized low-density lipoprotein to vascular wall cells. J Biol Chem 278:6187–6193

  56. 56.

    Weber C (2005) Platelets and chemokines in atherosclerosis: partners in crime. Circ Res 96:612–616

  57. 57.

    Nichols AB, Owen J, Kaplan KL, Sciacca RR, Cannon PJ, Nossel HL, Fibrinopeptide A (1982) Platelet factor 4, and beta-thromboglobulin levels in coronary heart disease. Blood 60:650–654

  58. 58.

    Kutti J, Svardsudd K, Sigvaldason A, Safai-Kutti S, Wadenvik H (1983) Plasma platelet factor 4: a potentially useful predictor of ischaemic heart disease? Folia Haematol Int Mag Klin Morphol Blutforsch 110:868–873

  59. 59.

    van Hulsteijn H, Kolff J, Briet E, van der Laarse A, Bertina R (1984) Fibrinopeptide A and beta thromboglobulin in patients with angina pectoris and acute myocardial infarction. Am Heart J 107:39–45

  60. 60.

    Files JC, Malpass TW, Yee EK, Ritchie JL, Harker LA (1981) Studies of human plate alpha-granule release in vivo. Blood 58:607–618

  61. 61.

    Caimi G, Hoffmann E, Montana M, Incalcaterra E, Dispensa F, D’Amico T, Canino B, Lo Presti R (2005) Plasma markers of platelet and polymorphonuclear leukocyte activation in young adults with acute myocardial infarction. Clin Hemorheol Microcirc 32:67–74

  62. 62.

    Snoep JD, Roest M, Barendrecht AD, de Groot PG, Rosendaal FR, van der Bom JG (2010) High platelet reactivity is associated with myocardial infarction in premenopausal women: a population-based case-control study. J Thromb Haemost 8(5):906–913

  63. 63.

    Smith C, Damas JK, Otterdal K, Oie E, Sandberg WJ, Yndestad A, Waehre T, Scholz H, Endresen K, Olofsson PS, Halvorsen B, Gullestad L, Froland SS, Hansson GK, Aukrust P (2006) Increased levels of neutrophil-activating peptide-2 in acute coronary syndromes: possible role of platelet-mediated vascular inflammation. J Am Coll Cardiol 48:1591–1599

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Acknowledgments

Dr Berger was partially funded by an American Heart Association Fellow to Faculty Award (0775074N) and a Doris Duke Clinical Scientist Award.

Author information

Correspondence to Jeffrey S. Berger.

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Sharma, G., Berger, J.S. Platelet activity and cardiovascular risk in apparently healthy individuals: a review of the data. J Thromb Thrombolysis 32, 201–208 (2011). https://doi.org/10.1007/s11239-011-0590-9

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Keywords

  • Platelet activity
  • Platelet aggregation
  • Mean platelet volume
  • Cardiovascular risk factor